Pharmacodynamic Changes of Mivacurium in Liver Cirrhosis Model in Rabbits Using Carbon Tetrachloride Intoxication

Abstract

Background: A reproducible animal model of liver cirrhosis by administering multiple doses of carbon tetrachloride () is highly desirable for appropriate metabolic and therapeutic studies. The current study was undertaken to evaluate the neuromuscular blockade of mivacurium in induced liver cirrhosis in rabbits. Methods: Cirrhosis was induced in rabbits by treatment for 11 weeks. Rabbits were randomly assigned to two groups;control group: corn oil 0.5 ml/kg/2 days IM for 11 weeks; study group: 0.5 ml/kg/2 days mixed 1：1 with corn oil IM for 11 weeks. In the first study, the dose-response relations of mivacurium were studied in twenty rabbits during thiopental anesthesia. They received mivacurium 10, 20, and 30/kg in control group, and mivacurium 20, 30, and 40/kg in study group, respectively. In the second study, time course of mivacurium 0.18 mg/kg in twenty rabbits was evaluated in each groups. Three fragments of each liver lobe at the end of the experimental period were performed for the histological examination. Results: Eleven-weeks treatment resulted in liver cirrhosis, decreased pseudocholinesterase to 1/6 of control level, and increased AST and ALT compared with controls. In the first study, There were significant differences between two groups. In the second study, There were significant differences between two groups. Conclusions: It is suggested that mivacurium should be used with caution in patients with hepatic insufficiency and that, in such patients, monitoring of neuromuscular function is desirable.